Prof. Dr hab. Maria Agnieszka Bzowska

Division of Biophysics
Institute of Experimental Physics
University of Warsaw
Zwirki i Wigury 93, 02-089 Warsaw, Poland

Phone: +48 22 5540789

E-mail: abzowska@biogeo.uw.edu.pl

Research interests

Enzyme structure and molecular mechanism, protein/ligand interactions, protein crystallography, molecular spectroscopy; recently also competition between protein folding and aggregation. Main achievement: determination of three-dimensional structure and elucidation of molecular mechanism of catalysis for purine nucleoside phosphorylases - key enzymes of the metabolic salvage pathway. Close cooperation with Beata Wielgus-Kutrowską and Jan Antosiewicz.

Professional experience

1984 Msc. in physics and biophysics, Faculty of Physics, Warsaw University, Warsaw, Poland
1984-1990 Department of Biophysics, Research and Teaching Assistant
1990 PhD in physics and biophysics, Faculty of Physics, Warsaw University, Warsaw, Poland
1990 - Department of Biophysics, Research and Teaching Associate
1993-2002 1-3 months per year, Visiting Scientist in the laboratory of Prof. Wolfram Saenger, Institut für Kristallographie, Freie Universität Berlin

Selected publications

  1. A. Bzowska, E. Kulikowska, D. Shugar, Properties of purine nucleoside phosphorylase (PNP) of mammalian and bacterial origin. Z. Naturforsch. 45c, 59-70 (1990).
    cited more than 50 times
  2. A. Bzowska, M. Luic, W. Schroder, D. Shugar, W. Saenger, G. Koellner, Calf spleen purine nucleoside phosphorylase: purification, sequence and crystal structure of its complex with N(7)-acycloguanosine inhibitor. FEBS Letters 367, 214-218 (1995).
    cited more than 40 times
  3. G. Koellner, M. Luić, D.Shugar, W. Saenger and A. Bzowska, Crystal structure of calf spleen purine nucleoside phosphorylase in a complex with hypoxanthine at 2.15 Ĺ resolution. J. Mol. Biol. 265, 202-216 (1997).
    cited more than 60 times
  4. G. Koellner, M. Luić, D. Shugar, W. Saenger and A. Bzowska, Crystal structure of the ternary complex of E. coli purine nucleoside phosphorylase with formycin B, a structural analogue of the substrate inosine, and phosphate (sulphate) at 2.1 Ĺ resolution. J. Mol. Biol. 280, 153-166 (1998).
    cited more than 50 times
  5. B. Wielgus-Kutrowska, J. Tebbe, J. Wierzchowski, D. Shugar, W. Saenger, G. Koellner and A. Bzowska, Binding of substrates by purine nucleoside phosphorylase (PNP) from Cellulomonas sp. - kinetic and spectrofluorimetric studies. Nucleosides and Nucleotides 18, 871-872 (1999).
  6. J. Tebbe, A. Bzowska, B. Wielgus-Kutrowska, W. Schröder, Z. Kazimierczuk, D. Shugar, W. Saenger, W. and G. Koellner, Crystal structures of purine nucleoside phosphorylase (PNP) from Cellulomonas sp. and its implications of the molecular mechanism of trimeric PNPs. J. Mol. Biol. 294, 1239-1255 (1999).
    cited more than 40 times
  7. A. Bzowska, E. Kulikowska, and D. Shugar, Purine nucleoside phosphorylase: properties, functions and clinical aspects. Pharmacology & Therapeutics 88, 349-425 (2000).
    cited more than 200 times
  8. M. Luić, G. Koellner, D. Shugar, W. Saenger and A. Bzowska, Calf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion. Acta Cryst. D57, 30-36 (2001).
  9. G. Koellner, A. Bzowska, B. Wielgus-Kutrowska, M. Luić, T. Steiner, W. Saenger and J. Stępiński, Open and closed conformation of the E. coli purine nucleoside phosphorylase active center and implications for the catalytic mechanism. J. Mol. Biol. 315, 351-371 (2002).
  10. A. Bzowska, Calf spleen purine nucleoside phosphorylase: complex kinetic mechanism, hydrolysis of 7-methylguanosine, and oligomeric state in solution. Biochim. Biophys. Acta 1596, 293-317 (2002).
  11. B. Wielgus-Kutrowska, A. Bzowska, J. Tebbe, G. Koellner and D. Shugar, Purine nucleoside phosphorylase from Cellulomonas sp.: physicochemical properties and binding of substrates determined by ligand-dependent enhancement of enzyme intrinsic fluorescence, and by protective effects of ligands on thermal inactivation of the enzyme. Biochim. Biophys. Acta 1597, 320-334 (2002).
  12. B. Wielgus-Kutrowska, A. Holy, J. Frank, G. Koellner and A. Bzowska, Interactions of trimeric purine nucleoside phosphorylases with ground state analogues - calorimetric and fluorimetric studies. Nucleosides, Nucleotides and Nucleic Acids 22, 1695-1698 (2003).
  13. A. Bzowska, G. Koellner, B. Wielgus-Kutrowska, A. Stroh, G. Raszewski, A. Holý, T. Steiner, J. Frank, Crystal structure of calf spleen purine nucleoside phosphorylase with two full trimers in the asymmetric unit: important implications for the mechanism of catalysis. J. Mol. Biol. 342, 1015-1032 (2004).
  14. M. Luić, G. Koellner, T. Yokomatsu, S. Shibuya and A. Bzowska, Calf spleen purine-nucleoside phosphorylase: crystal structure of the binary complex with a potent multisubstrate analogue inhibitor. Acta. Cryst. D 60, 1417-1424 (2004).
  15. J. Wierzchowski, A. Bzowska, K. Stępniak, D. Shugar, Interactions of calf spleen purine nucleoside phosphorylase with 8-azaguanine, and a bisubstrate analogue inhibitor: implications for the reaction mechanism. Z. Naturforsch. 59c, 713-725 (2004).
  16. B. Wielgus-Kutrowska, A. Bzowska, Kinetic properties of Cellulomonas sp. purine nucleoside phosphorylase with typical and non-typical substrates: implications for the reaction mechanism. Nucleosides, Nucleotides and Nucleic Acids 5-7, 471-476 (2005).
  17. K. Banach, E. Bojarska, Z. Kazimierczuk, L. Magnowska, A. Bzowska, Kinetic model of oxidation catalyzed by xanthine oxidase - the final enzyme in degradation of purine nucleosides and nucleotides. Nucleosides, Nucleotides and Nucleic Acids 5-7, 465-469 (2005).
  18. M. Długosz, A. Bzowska, J, Antosiewicz, Stopped-flow studies of guanine binding by calf spleen purine nucleoside phoshorylase. Biophys. Chem. 115, 67-76 (2005).
  19. J. Behlke, G. Koellner, A Bzowska, Oligomeric structure of mammalian purine nucleoside phosphorylase in solution determined by analytical ultracentrifugation. Z. Naturforsch. 60c (2005).
  20. B. Wielgus-Kutrowska, A. Bzowska, Probing the mechanism of purine nucleoside phosphorylase by steady-state kinetic studies and ligand binding characterization determined by fluorimetric titrations. Biochim. Biophys. Acta 1764, 887-902 (2006).
  21. A. Modrak-Wójcik, K. Stepniak, V. Akoev, M. Żółkiewski, A. Bzowska, Molecular architecture of E. coli purine nucleoside phosphorylase studied by analytical ultracentrifugation and CD-spectroscopy. Prot. Sci. 15, 1794-1800 (2006).
  22. B. Wielgus-Kutrowska, J. Antosiewicz, M. Długosz, A. Holý, A. Bzowska, Towards the mechanism of trimeric purine nucleoside phosphorylases: stopped-flow studies of binding of multisubstrate analogue inhibitor - 2-amino-9-[2-(phosphonomethoxy)-ethyl]-6-sulfanylpurine. Biophys. Chem. 125, 260-268 (2007).
  23. B. Wielgus-Kutrowska, M. Narczyk. A. Buszko, A. Bzowska, P. Clark, Folding and unfolding of non-fluorescent mutant of green fluorescent protein. J. Phys.: Condens. Matter 19, 285223 (2007).
  24. A. Modrak-Wójcik, K. Stepniak, B. Kierdaszuk, A. Bzowska, Is purine nucleoside phosphorylase an example of a morpheein? J. Phys.: Condens. Matter, 19, 285219 (2007).
  25. K Breer, A. Girstun, B. Wielgus-Kutrowska, K. Staroń, A. Bzowska, Overexpression, purification and characterization of functional calf purine nucleoside phosphorylase (PNP). Protein Expr Purif. 61, 122-130 (2008).
  26. J. Antosiewicz, K Breer, A. Bzowska, B. Wielgus-Kutrowska, On the analysis of fluorimetric titration curves of purine nucleoside phosphorylase. Nucleic Acids Symp Ser (Oxf) 52, 671-672 (2008).
  27. A. Bzowska, L Magnowska, Simple and universal method to determine dissociation constants for enzyme/ligand complexes. Nucleic Acids Symp Ser (Oxf) 52 669-670 (2008).
  28. A. Bzowska, Formycins and their analogues: purine nucleoside inhibitors and their applications in immunosuppression and cancer., in .Modified nucleosides. P. Herdewijn, ed., Wiley (2008).
  29. K. Breer, B. Wielgus-Kutrowska, A. Girstun, K. Staron, M. Hashimoto, S. Hikishima, T. Yokomatsu, A. Bzowska, Overexpressed proteins may act as mops removing their ligands from the host cells: a case study of calf PNP, BBRC, 391, 1203-1209 (2010).
  30. G. Chojnowski, K. Breer, M. Narczyk, B. Wielgus-Kutrowska, H. Czapinska, M. Hashimoto, S. Hikishima, T. Yokomatsu, M. Bochtler, A. Girstun, K. Staron, A. Bzowska, 1.45 . resolution crystal structure of recombinant PNP in complex with a pM multisubstrate analogue inhibitor bearing one feature of the postulated transition state, BBRC, 391, 703-708 (2010).
  31. S. Hikishima, M. Hashimoto, L. Magnowska, A. Bzowska, T. Yokomatsu, Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs, Bioorg. Med. Chem. 18, 2275-2284 (2010).
  32. L. Glava1-Obrovac, M. Suver, Sadao Hikishima, M. Hashimoto, T. Yokomatsu, L. Magnowska, A. Bzowska, Antiproliferative Activity of Purine Nucleoside Phosphorylase Multisubstrate Analogue Inhibitors Containing Difluoromethylene Phosphonic Acid against Leukemia and Lymphoma Cells, Chemical Biology and Drug Design 76, 392-399 (2010).
  33. K. Breer, L. Glava1-Obrovac, M. Suver, S. Hikishima, M. Hashimoto, T. Yokomatsu, B. Wielgus-Kutrowska, L. Magnowska, A. Bzowska, 9-Deazaguanine derivatives connected by a linker to difluoromethylene phosphonic acid are slow-binding picomolar inhibitors of trimeric purine nucleoside phosphorylase, FEBS Journal 277, 1747-1760 (2010).
  34. J. Krasowska, M. Olasek, A. Bzowska, P.L. Clark, B. Wielgus-Kutrowska, The comparison of aggregation and folding of enhanced green fluorescent protein (EGFP) by spectroscopic studies, Spectroscopy 24, 343-348 (2010).
  35. G. Mikleusević, Z. Stefanić, M. Narczyk, B. Wielgus-Kutrowska, A. Bzowska, M. Luić, Validation of the catalytic mechanism of Escherichia coli purine nucleoside phosphorylase by structural and kinetic studies, Biochimie 93, 1610-1622 (2011).
  36. Z. Stefanic, M. Narczyk, G. Mikleusevic, B. Wielgus-Kutrowska, A. Bzowska, M. Luic, New phosphate binding sites in the crystal structure of Escherichia coli purine nucleoside phosphorylase complexed with phosphate and formycin A, FEBS Letters 586, 967-971 (2012).
  37. B.Wielgus-Kutrowska, K. Breer, M. Hashimoto, S. Hikishima, T. Yokomatsu, A. Dyzma, M. Narczyk, A. Girstun, K. Staroń, A. Bzowska, Trimeric purine nucleoside phosphorylase: exploring postulated one-third-of-the-sites binding in the transition-state, Bioorg Med Chem. 20, 6758-6769 (2012).
  38. Z. Stefanić, G. Mikleusević, M. Narczyk, B. Wielgus-Kutrowska, A. Bzowska, M. Luić, Still a long way to fully understanding the molecular mechanism of Escherichia coli purine nucleoside phosphorylase, Croat. Chem. Acta 86, 117-127 (2013).

Participation in research projects

  1. Biophysical bases of purine nucleoside phosphorylase mechanism, and synthesis and biological evaluation of inhibitors - potential drugs.
  2. Mechanism of binding of ligands and communication between purine nucleoside phosphorylase subunits - investigations of mutants with changed fluorescence properties.
  3. De novo folding of Green Fluorescent Protein in the aspect of applications in biotechnology and molecular biology.
  4. Homooligomeric enzymes with very strong cooperation in ligands binding.